Fig. 8: Graphical abstract summarizing the main findings.

We have characterized the function of the PGPH enzymes in C. elegans. PGPH enzymes act as glycerol-3-phosphate phosphatase (G3PP) and are responsible for glycerol production via the direct hydrolysis of glycerol-3-phosphate. Loss of PGPH enzymes decreases resistance to diverse stresses, shortens lifespan and healthspan and exacerbates glucotoxicity. In contrast, the overexpression of PGPH-2, mimics calorie restriction without changes in food intake and fertility, decreases fat deposition, protects from glucose-induced toxicity and promotes healthy aging. Overall, the results identify G3PP as a candidate therapeutic avenue to treat obesity and age-related cardiometabolic disorders, and to promote healthy aging.